tbuckley/cabot-search huggingface dataset:
Patient and caregiver-reported acceptability of an automatic phone call offering supportive and palliative care referral for advanced non-small cell lung cancer patients.
Authors: Aliyah Pabani, Seema King, Sadia Ahmed, Lisa Shirt, Vanessa Slobogian, Chandra Vig, Desiree Hao, Lisa Catherine Barbera, Elizabeth Kurien, Maria Santana, Patricia Biondo, Aynharan Sinnarajah, Jessica Simon
Journal: Journal of Clinical Oncology (2022)

e24097 Background: Timely palliative care interventions can help to alleviate the distress people experience after a diagnosis of an incurable, life-threatening cancer. However, referrals to palliative care continue to be late due to various provider and patient barriers. The Palliative Care Early and Systematic (PaCES)-Automatic study was co-designed with patients and providers and implemented an early palliative care intervention for newly diagnosed stage IV non-small lung cancer (NSCLC). The objective of this study was to determine patient/caregiver-reported acceptability of a phone call from a supportive and palliative care (SPC) nurse offering consultation, automatically (without referral) after first oncologist appointment. Methods: Two SPC specialist nurses screened out-patient clinic lists at a tertiary cancer center weekly and called all eligible patients offering an in-home consultation. Eligibility: &gt; 18 years, newly diagnosed/suspected Stage IV NSCLC and had first medical/radiation oncologist visit. Patients/caregivers were surveyed about the acceptability (5-point Likert scale) of the automatic phone call offering a palliative care consult, using Sekhon’s Framework of Acceptability domains. Results: Among the 113 patients screened, 81 patients/caregivers were contacted and offered SPC consultation and 72% accepted the in-home consult. Of 70 patients/caregivers that agreed to be contacted for the survey: 4 did not recall the call offering SPC, 3 declined participating in the survey, and 15 were not reached. Of 48 respondents, 93.6% rated overall acceptability of the automatic call offering SPC consultation somewhat/completely acceptable, with the other 6.4% rating it as neither acceptable nor unacceptable. Of 35 patients/caregivers that completed the full survey: 31% caregivers, 63% female, 57% ≤65 years, 29% ≤high school education, 67% (n = 27) &lt; $60,000 household income, 80% spoke only English/French, and 71% Caucasian. Within the domains of acceptability, 94.7% were comfortable receiving the call, 91.9% understood why they received it; 86.5% thought the call was a valuable; 69.5% thought the call helped them; 65.7% learned about SPC from the call; no one expressed concern that the SPC nurse had access to their contact/health information; 97.2% thought the call didn’t take much physical/emotional effort and were confident in their ability to participate (ask questions/make decisions). Conclusions: Nearly all patients/caregivers found the automatic SPC call offering consultation to be acceptable. Most patients agreed to the consultation offer. Routine calls offering SPC consultation may be a timely alternative to awaiting conventional referral by oncologists.
Utilization of immortalized B cells to identify SDCBP as a novel therapeutic target in ovarian carcinoma.
Authors: Katelyn Handley, Sumit Mehta, Alexandra Martin, Subir Biswas, Kamira Karen Maharaj, Jessica A. Mine, Carla Cortina, Mate Nagy, Kimberly Sprenger, Gunjan Mandal, Patrick Innamarato, John Joseph Powers, Carly M. Harro, Ricardo A. Chaurio, Carmen M. Anadon, Javier Pinilla-Ibarz, Mian M. Shahzad, Idhaliz Flores, Jose Conejo-Garcia
Journal: Journal of Clinical Oncology (2022)

e14507 Background: We hypothesized that tumor-infiltrating B cells in endometriosis and endometriosis-associated ovarian cancer can be used to identify novel, targetable antigen domains to inhibit the progression of ovarian carcinomas. We aimed to identify targets that are spontaneously recognized by B-cell-derived antibodies within ovarian clear cell carcinoma (CCC), endometrioid carcinoma (EC), and endometriosis and to determine the preclinical anti-cancer efficacy of a candidate antibody that recognizes the extracellular domain of an identified target. Methods: B cells from freshly dissociated CCC (n = 2), EC (n = 2), and endometriomas (n = 2) were isolated, activated, and EBV-immortalized. Antibodies were purified from B cell supernatants and used for screening in a proteome array. Targets were prioritized based on accessibility (transmembrane or secreted proteins), expression in endometriosis and cancer, and concurrent IgA and IgG responses. Tumor-promoting syndecan binding protein (SDCBP) was identified and SDCBP-reactive B cells were FACS-sorted and subjected to single cell B cell receptor sequencing to determine the variable heavy and light chain sequences of enriched clonotypes. We then generated a recombinant IgG4 antibody targeting SDCBP with the dominant VH/VL matching sequences. Immunoblots and qPCR were performed to assess SDCBP expression in ovarian cancer cell lines and tumor samples. In vivo studies compared anti-tumor potential of the α-SDCBP IgG4 with controls using immunodeficient mouse models of human CCC and high-grade serous ovarian carcinoma (HGSOC). Results: Nine accessible proteins were detected by both IgA and IgG in all samples, including SDCBP. SDCBP is expressed in ovarian cancer cell lines and tumor samples of multiple histologies, including CCC, EC, and HGSOC. Administration of α-SDCBP IgG4 in TOV21G (CCC) tumor-bearing mice significantly decreased tumor volume compared to non-antigen-specific irrelevant IgG4 (iIgG4, p = 0.002) and vehicle (0.001), and correspondingly trended toward decreased tumor weight compared to vehicle (p = 0.06). Likewise, administration of α-SDCBP IgG4 in OVCAR3 (HGSOC) tumor-bearing mice significantly decreased tumor volume compared to iIgG4 (p = 0.03) and trended toward decreased tumor weight (p = 0.06). Conclusions: An α-SDCBP IgG4 has demonstrated anti-tumor efficacy in SDCBP + CCC and HGSOC, and SDCBP-targeted therapy for endometriosis and associated malignant conditions, as well as HGSOC, warrants further investigation.
Homologous recombination pathway alternations in relation to prognosis of MSS/pMMR colorectal cancer patients treated with immune checkpoint inhibitors (ICIs).
Authors: Xing Liu, Zhichao Fu
Journal: Journal of Clinical Oncology (2022)

e15517 Background: Colorectal cancer is a common malignant tumor in the gastrointestinal tract and represents the third deadliest cancer worldwide. Recently, the advent of immune checkpoint inhibitors (ICIs) has provided significant survival benefit for colorectal cancer(CRC) patients with MSI-H/dMMR. However, the majority of MSS/pMMR CRC patients show poorly durable responses of immunotherapy, and more proper predictive biomarker is required to guiding immunotherapy treatment for these CRC cancer patients. The purpose of the present study was to explore the role of Homologous recombination (HR) pathway alternations in predicting the prognosis of MSS/pMMR CRC patients treated with ICIs. Methods: All data of patients undergoing immunotherapy were obtained from the cBioPortal database (https://www. cbioportal.org), which include genomic sequencing datasets and clinical data for eight diverse cancers from MSKCC, and RNAseq data and clincial data for CRC from International Cancer Genome Consortium (TCGA). Results: In the MSKCC cohort, HR mutation was analyzed by univariate Cox regression in nine different cancers, the analysis performed revealed HR mutation were associated with a better prognosis of colcrectal cancer (p = 0.003; HR, 0.24; 95%Cl, 0.09-0.62) and melanoma (p = 0.042; HR,0.66; 95% Cl, 0.09-0.62), with no significant correlations in other cancers. By doing survival analysis of the CRC patients without MSI-H/dMMR status by Kaplan–Meier (KM) method. The results showed that the OS of the patients with HR-MT was signifcantly longer than that of patients with HR-WT (P = 0.0029), and no significance association has been identified between Tumor Mutational Burden (TMB) and overall prognosis of patients without MSI-H/dMMR. Notably, in TCGA CRC dataset, we found TMB and Neoantigens were significantly higher in HR-MT patients than that of HR-WT patients(p &lt; 0.0001), and a higher-level expression of CD8 T cell were also observed in the HR-MT patients patients in TCGA dataset (p = 0.036). Conclusions: Our study results showed that HR-mutation is a favorable prognostic factor in these CRC patients with MSS/pMMR, which can be used as a potential biomarker for predicting the immunotherapy efficacy of these patients.
Cross-trial validation of molecular subtypes in patients with metastatic clear cell renal cell carcinoma (RCC): The JAVELIN Renal 101 experience.
Authors: Renee Maria Saliby, Tejas Jammihal, Chris Labaki, Wanling Xie, Robert J. Motzer, Thomas Powles, Brian I. Rini, Laurence Albiges, Sumanta K. Pal, Rana R. McKay, Sabina Signoretti, Sachet A. Shukla, Eliezer Mendel Van Allen, David A. Braun, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2022)

4531 Background: Vascular endothelial growth factor (VEGF) and immune checkpoint inhibitors (IO) combinations are a standard in mRCC. Molecular clusters of patients have been identified and correlated with outcomes in the phase 3 IMmotion151 (IM151) trial of atezolizumab + bevacizumab (IO+VEGF) vs. sunitinib (Sun) (Motzer, Cancer Cell 2020 &amp; JAMA Oncol 2021). Avelumab+axitinib (AA) is an approved IO+VEGF combination in mRCC. This work aims to evaluate these clusters in patients from the phase 3 JAVELIN Renal 101 (JR101; NCT02684006 ) trial of AA vs. Sun. Methods: Bulk RNA-sequencing of primary and metastatic samples and clinical data (data cutoff: 28 January 2019) from JR101 were obtained. A random forest model designed to predict molecular clusters based on transcriptomic data was trained on the IM151 dataset. Using this model, patients from JR101 study were categorized into previously defined molecular subgroups. We then evaluated treatment outcomes including progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) from JR101 in relation to molecular subgroups. Results: The proportion of patients in each molecular subtype and across MSKCC risk groups were largely comparable between the 2 trials (accuracy: 81.6%; p=0.2). AA was generally superior to Sun. for PFS and ORR across all molecular subsets, including angiogenic and immune-based clusters (Table). Combining immune and/or cell cycle-enriched clusters 4+5 resulted in improved PFS (HR: 0.65; 95% CI: 0.44-0.97) for AA vs. Sun. Conclusions: We were able to largely validate the molecular clusters classification and some of the associations with survival outcomes from IM151 in the JR101 clinical trial cohort. Biomarkers of specific VEGF+IO combinations in mRCC should be prospectively validated in randomized trials. [Table: see text]
Efficacy and safety of IBI110 (anti-LAG-3 mAb) in combination with sintilimab (anti-PD-1 mAb) in first-line advanced squamous non-small cell lung cancer (sqNSCLC): Initial results from a phase Ib study.
Authors: Caicun Zhou, Anwen Xiong, Wei Li, Lei Wang, Fengying Wu, Jia Yu, Chenyu Mao, Jiong Qian, Yulong Zheng, Haiping Jiang, Yuan Gao, Cheng Xiao, Wenxiang Wang, Wu Zhuang, Jun Yang, Jiya Sun, Hongli Wang, Ying Liu, Nong Xu
Journal: Journal of Clinical Oncology (2022)

e21145 Background: Although PD-1/L1 inhibitors have shown efficacy in advanced/metastatic sqNSCLC, many patients do not respond to this treatment. More effective combination therapies are needed. The efficacy and safety of IBI110 in combination with sintilimab as first-line therapy for advanced sqNSCLC was evaluated in a phase Ib study. Here, we report the initial results. Methods: Eligible patients with previously untreated, unresectable, locally advanced or metastatic NSCLC were enrolled in cohort D. Patients received IBI110 200mg IV Q3W and sintilimab 200mg IV Q3W until disease progression, unacceptable toxicity or death, in combination with chemo regimen (paclitaxel 175 mg/m 2 plus carboplatin) IV Q3W for 4 cycles. The primary objective was to evaluate the safety, tolerability and efficacy of the combination therapy. Results: Totally, 20 patients were enrolled (median age: 63 [range: 52-74]; male: n = 19; ECOG 1: n = 16). As of data cutoff date, Jan 20, 2022, median follow up was 3.3 months (range: 2.6-7.0). The median exposure of combination therapy was 15.1 weeks (range: 6-52). The objective response rate was 80% (16/20, 9 patients with ≥2 efficacy assessments were confirmed PR and 7 needed further confirmation). The median progression-free survival and overall survival were not reached. The most common treatment-related adverse events (TRAEs) included white blood cell count decreased (50%), alopecia (50%), anaemia (45%), asthenia (40%), neutrophil count decreased (35%), rash (35%), and hyperglycaemia (30%); most common TRAEs ≥ grade 3 were neutrophil count decreased (30%), and white blood cell count decreased (20%). Immune-related AEs occurred in 11 patients (55%) and most were grade 1-2. The biomarker analysis including LAG-3 and PD-L1 expression in tumor specimen was ongoing. Conclusions: IBI110 in combination with sintilimab in first-line advanced sqNSCLC showed promising anti-tumor activity with acceptable safety. The study is still ongoing. Clinical trial information: NCT04085185.
Analysis of patient (pt) withdrawal of consent using 11,993 pts from 58 alliance for clinical trials in oncology trials.
Authors: Sumithra J. Mandrekar, Shauna L Hillman, Carrie Strand, David Zahrieh, Suzanne George, Aminah Jatoi
Journal: Journal of Clinical Oncology (2022)

6513 Background: Pt recruitment receives well-deserved attention, but pt retention is also important for trial interpretability and generalizability. We report on trends and predictive factors for withdrawal of pt consent, defined as pt cessation from trial participation for reasons not mandated in the protocol. Methods: Alliance phase II/III trials that enrolled pts during 2013 – 2019 were included. All pts had ≥2 years (yrs) of follow-up. Primary outcome was withdrawn consent (yes; no) within 2 yrs of enrollment. Pt factors included year of enrollment, age, race, ethnicity, and gender. Trial factors included randomization, use of placebo, and use of radiation. Univariable (Uni) and full multivariable (MV) logistic regression models (including all factors from Uni setting) with a Bonferroni p-value correction (p &lt;.004 considered significant) were used. Results: Median age was 62 yrs, with 67% female, 82% White, 9% Black or African American, and 7% Hispanic. 52% of trials were phase II, 5% II/III and 43% III. Common (&gt; 10%) trial categories included 22% experimental therapeutics or rare tumors, 12% gastrointestinal, 12% genitourinary, 12% neuro-oncology and 10% symptom intervention. 78% of trials were randomized, 22% placebo-controlled and 14% used radiation. 1060 (9%) pts withdrew consent within 2 yr of enrollment (range,5.7% -9.8%) during 2013-2019. In Uni models, all trial and pt factors significantly predicted pt withdrawal except age, race, and gender (See table). In MV models, pts of Hispanic origin, and &gt;75 yrs were more likely to withdraw. Trials using radiation had less likelihood of pt withdrawal. Placebo-controlled randomized trials had higher likelihood of withdrawal. Conclusions: Both trial and pt factors contribute to higher rates of pt withdrawal from clinical trials. Understanding these factors will enable investigators to focus on pt education and optimization of trial design to improve pt retention and the overall clinical trial plan. Support: U10CA180821, U10CA180882 [Table: see text]
Prevalence and survival of gastrointestinal malignancies with brain metastasis: Surveillance, Epidemiology, and End Results SEER database analysis 2010-2018.
Authors: Akram Alkrekshi, Dina Elantably, Faris Hammad, Abdul Rahman Al Armashi
Journal: Journal of Clinical Oncology (2022)

e14004 Background: Gastrointestinal (GI) cancers are amongst the leading causes of cancer-related death worldwide. GI cancers with brain metastasis on presentation are rare; however, the oncologist will intermittently encounter such patients. Unfortunately, there is a paucity of data to inform the prevalence and prognosis of GI cancers with brain metastasis, especially in light of therapeutic developments in the past decade and whether that might have influenced the survival. In this study, we measured the prevalence of brain metastasis secondary to primary GI malignancies at the time of diagnosis, the observed median survival, and Kaplan-Meier 2-years overall survival. The aim is to highlight the burden and prognosis of this population. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) Program 18 registry (2010-2018) database. We identified the total number of patients and patients with brain metastasis at the time of diagnosis for the following gastrointestinal cancers: esophagus, stomach, pancreas, colon, rectum, liver, intrahepatic biliary duct, and gallbladder. We obtained the prevalence, the observed median survival, and the 2-years survival using the Kaplan-Meier method. Results: The total number of cases, prevalence, median survival, and 2-years overall survival are shown in the table. The prevalence of brain metastasis at diagnosis was highest for esophageal cancer at 1.41%, followed by stomach 0.52%, and gall bladder 0.37%. The lowest incidence was small intestinal cancers at 0.13%. The median survival was short, ranging between 2 to 4 months for all studied cancers except for the small intestine and rectum at about six months. Kaplan-Meier 2-years survival was highest for the small intestine at 17%, and the worst was gallbladder, where no one survived at the end of the 24 months. Conclusions: Brain metastasis at the time of diagnosis of GI cancer remains rare. However, its presence portends an abysmal prognosis of 2-4 months. This study helps to inform the practicing oncologist of the current prevalence and prognosis of GI malignancies with brain metastasis on presentation. In addition, these findings encourage prompt involvement of palliative care, setting realistic expectations, and discussing goals of care once such a grave diagnosis is made.[Table: see text]
Efficacy and safety of autologous expanded tumor infiltrating lymphocytes (TILs) in multiple solid tumors.
Authors: Rodabe Navroze Amaria, David J. Vining, Scott Kopetz, Michael J. Overman, Milind M. Javle, Mara Antonoff, Ching-Wei D. Tzeng, Robert A. Wolff, Shubham Pant, Kathryn Lito, Kelly M. Rangel, Louis Wilson, Bryan M. Fellman, Cara L. Haymaker, Ying Yuan, Marie-Andree Forget, Patrick Hwu, Chantale Bernatchez, Amir A. Jazaeri
Journal: Journal of Clinical Oncology (2022)

2536 Background: TIL therapy has been used extensively in metastatic melanoma patients for many years, now with ongoing efforts to commercialize treatment. The efficacy of TIL outside of melanoma is largely unknown thus we designed and implemented a trial using TIL manufactured at a single academic center for treatment refractory metastatic colorectal (CRC), pancreas (PDAC) and ovarian (OVA) cancers. Methods: Patients with CRC, PDAC and OVA refractory to standard therapies with ECOG PS 0-1 and normal organ function were eligible for TIL harvest. Ex vivo TIL expansion and manufacturing was conducted at the MD Anderson TIL lab under conditions that included IL2 and 41BB stimulation (using urelumab). All patients received a lymphodepletion regimen consisting of cyclophosphamide 60mg/kg days -7 and -6 and fludarabine 25mg/m2 days -5 through day -1, followed by infusion of pooled ex-vivo expanded TIL. Patients received up to 6 doses of high dose IL-2 (600,000 IU/kg) after TIL infusion. The primary endpoint was evaluation of the objective response rate (ORR) using RECIST 1.1 criteria with secondary endpoints including disease control rate, duration of response, PFS, OS and safety. Results: A total of 17 patients underwent TIL harvest and 16 were treated on protocol; including 8 CRC, 5 PDAC and 3 OVA. Median age was 57.5 (range 33-70) and 50% were females. Median number of lines of prior therapy was 2 (range 1-8). Median number of TIL infused was 76 X 10 9 (range 20.3 x 10 9 -150 x 10 9 ). Median doses of cyclophosphamide and fludarabine administered were 2 (range, 2-2) and 3 (range, 1-5), respectively. Median doses of IL-2 administered was 6 (range, 1-6). There were no responders. Best response included prolonged SD in a patient with PDAC lasting until 18 months. Grade 3 or higher toxicities attributable to therapy was seen in 14 subjects (87.5%; 95% CI: 61.7 – 98.4) with the majority of toxicities representing expected pancytopenia from lymphodepletion. Infusion product analysis showed the presence of effector memory cells with high expression of CD39 irrespective of tumor type. Early on-treatment biopsy of PDAC patient with prolonged SD showed presence of proliferating (KI67+) CD4+ and CD8+ TIL. Conclusions: Generation of TIL at a single academic center for CRC, PDAC and OVA is feasible and treatment is associated with no new safety signals. For these tumor types, further research is required to identify host factors associated with resistance to TIL therapy and optimize manufacturing processes to create more effective TIL cell therapy. Clinical trial information: NCT03610490.
Self-reported financial difficulties among patients with multiple myeloma and chronic lymphocytic leukemia: An Alliance for Clinical Trials in Oncology study.
Authors: Rena M. Conti, Shaylene McCue, Travis Dockter, Stacie Dusetzina, Bruce D. Rapkin, Elisa S. Weiss, Robert J. Behrens, Paul G. Richardson
Journal: Journal of Clinical Oncology (2022)

6602 Background: Treatment advances have greatly improved survival and quality of life among blood cancer patients, yet significant financial costs are a growing concern. Methods: We conducted an observational, prospective survey in 2019-2020 to estimate the self-reported prevalence of financial difficulty among multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients and identify sociodemographic correlates of financial difficulty. Patients with an MM or CLL diagnosis &gt;/= 18 years of age were recruited from NCI NCORP sites of care. Financial difficulty was measured in a previously validated single question from the EORTC QLQ C30 and a composite measure of five questions from the EORTC QLQ C30. Results: 521 MM and CLL patients were registered to the study, 416 patients were administered all or part of the patient survey, for an overall response rate of 79.8%. 16.8% of respondents reported experiencing financial difficulty in response to the single item question and 58.6% reported experiencing financial difficulty in response to the composite measure. Respondents reporting financial difficulty to both measures had reported household incomes of less than $60,000, identified their highest education levels as a high school diploma or GED, had more than one medical comorbidity and used an expensive oral chemotherapeutic agent to treat their blood cancer. Conclusions: Blood cancer patients treated at NCI NCORP sites are experiencing financial difficulties. Results of this study aim to inform physician, site of care and policy efforts to improve access among cancer patients. Clinical trial information: NCT03870633. [Table: see text]